A genetic screen for new Polycomb group genes in Drosophila melanogaster and biochemical purification of novel PcG protein complexes

果蝇同源异型基因的抑制Polycomb组蛋白提出了一个范例，在发展过程中的遗传基因沉默。在早期的果蝇胚胎中，局部阻遏物决定了同源异型基因在哪些片段中必须保持不活动。在随后的发育过程中，同源异型基因在这些片段衍生的细胞中保持遗传沉默，即使早期的阻遏物不再存在。这种可遗传的沉默需要Polycomb组的蛋白质。在果蝇中已经鉴定了几个Polycomb组基因，但是没有进行Polycomb组突变体的系统筛选。值得注意的是，似乎尚未发现在沉默过程中具有重要作用的多梳组基因。在这里，我建议使用遗传筛选，以确定新的Polycomb组基因在果蝇。简而言之，我们将进行饱和诱变，以筛选具有Polycomb样表型的成体表皮克隆中的新突变体。长期目标是绘制和克隆这些新的Polycomb组基因。Polycomb族蛋白在脊椎动物中结构和功能都是保守的，一些Polycomb族蛋白在植物发育中起阻遏物的作用。因此，在果蝇中鉴定新的Polycomb组基因可能会对理解其他生物中的表观遗传沉默过程产生影响。

Repression of Drosophila homeotic genes by Polycomb group proteins presents a paradigm for heritable gene silencing during development. In the early Drosophila embryo, localized repressors determine in which segments homeotic genes must remain inactive. During subsequent development, homeotic genes stay heritably silenced in the cells derived from these segments even though the early repressors are no longer present. This heritable silencing requires the proteins of the Polycomb group. Several Polycomb group genes have been identified in Drosophila but no systematic screens for Polycomb group mutants have been performed. Notably, it appears that several Polycomb group genes with important roles in the silencing process have not been discovered yet. Here, I propose to use a genetic screen to identify novel Polycomb group genes in Drosophila. In brief, we will perform a saturation mutagenesis to screen for new mutants with Polycomb-like phenotypes in clones in the adult epidermis. The long-term aim will be to map and clone these new Polycomb group genes. Polycomb group proteins are conserved in both structure and function in vertebrates and several Polycomb group proteins function as repressors in plant development. It is therefore likely that the identification of new Polycomb group genes in Drosophila will have impacts for understanding epigenetic silencing processes in other organisms.